Desvenlafaxine in the form of hydrogen succinate of formula (IV), i.e. a salt with the molar proportion of desvenlafaxine base:succinic acid of 1:1, was approved for treatment of depression and vasomotor symptoms related to the menopause (Drugs of the Future 2006, 31(4), 304-309).

U.S. Pat. No. 4,535,186 in Example 19 describes preparation of desvenlafaxine by debenzylation of the starting “O-benzyldesvenlafaxine”, Scheme 1.

Desvenlafaxine prepared in this manner in the free base form is transformed by the effect of fumaric acid in an acetone—ethanol mixture to a salt characterized by the melting point of 140-142° C.
Other patented procedures (e.g. U.S. Pat. Nos. 7,026,508, 6,673,838, WO 03/048104, WO 2007/071404, WO 2007/120923) describe preparation of the desvenlafaxine base by demethylation of venlafaxine; Scheme 2. Thiolates or trialkylborohydrides, for example, are used as demethylation agents.

Patent no. WO 00/76955 in Example 1 describes transformation of the crude base of Desvenlafaxine to the hydrogen fumarate hydrate of formula (V), i.e. a salt with the molar proportion of desvenlafaxine base:fumaric acid of 1:1: from a methanol/acetone mixture with a small addition of water. The salt is characterized by the melting point of 145-150° C.

U.S. Pat. Nos. 7,026,508 and 6,673,838 mention that the hydrogen fumarate has unsuitable physical and chemical properties, e.g. solubility. For this reason this patent claims the hydrogen succinate, including its several polymorphous forms and hemisuccinate. U.S. Pat. No. 7,001,920 describes preparation of desvenlafaxine formate, which also has more suitable physical and chemical properties than the hydrogen fumarate according to the authors.